Hemolysis of erythrocytes by primary pharmacologic agents, part 2: influence of the vehicle.

The hemolytic activity in vitro of chlorpromazine hydrochloride, chlordiazepoxide hydrochloride and brompheniramine maleate was examined using various intravenous solutions as the vehicle. Fresh human blood was employed in the investigation which used a colorimetric method for the determination of hemolysis. Prior to the examination of the hemolytic activity of each drug in the various vehicles, the vehicles themselves were examined for their ability to protect erythrocytes from hemolysis. Little to no hemolysis occurred in normal saline solution (the standard), dextrose 2.5% in normal saline, dextrose 5% in normal saline, dextrose 10% in normal saline, and lactated Ringer's injection. Low levels of hemolysis occurred in dextrose 5% in water, invert sugar 10% in water, and M/6 sodium lactate in water. High levels of hemolysis occurred when red blood cells were suspended in dextrose 2.5% in water. Invert sugar 10% in normal saline and fructose 10% in water caused red cell denaturation resulting in brown cells and hemolysate rather than the characteristic red color. This denaturation was attributed to the hydrogen ion concentration of these two solutions, both having pH values less than 4.0. Vehicles of dextrose in saline, dextrose in water, lactated Ringer's, and invert sugar in water reduced the level of drug-induced hemolysis for the drugs tested compared to that which occurred in normal saline solution. The reduction of hemolysis was greater as the tonicity of the vehicle used was increased. It was concluded that the pharmaceutical vehicles examined have an influence on the cellular effects of drugs which only affects the erythrocyte but which could potentially affect the drugs' distribution from the blood to the sites of their action.